Mitochondria-targeted antioxidant preserves contractile properties and mitochondrial function of skeletal muscle in aged rats.
Mitochondria-targeted antioxidant preserves contractile properties and mitochondrial function of skeletal muscle in aged rats.
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靶向线粒体的抗氧化剂可保留老年大鼠骨骼肌的收缩特性和线粒体功能。
DOI：
10.18632/oncotarget.5783
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发表时间：
2015-11-24
期刊：
影响因子：
--
通讯作者：
Frontera W
中科院分区：
文献类型：
--
作者：
Javadov S;Jang S;Rodriguez-Reyes N;Rodriguez-Zayas AE;Soto Hernandez J;Krainz T;Wipf P;Frontera W
线粒体功能障碍在骨骼肌质量和活动减少相关的肌少症发病机制中起核心作用。除了能量剥夺外，线粒体ROS增加还会损伤老年骨骼肌中的蛋白质和脂质。因此，预防线粒体ROS对于延缓肌肉减少症的潜在治疗策略非常重要。本研究阐明了新开发的线粒体靶向ROS和电子清除剂XJB-5-131 （XJB）在恢复老年骨骼肌肌肉收缩力和线粒体功能方面的药理作用。雄性成年（5月龄）和老年（29月龄）Fischer Brown Norway （F344/BN）大鼠用XJB治疗4周，治疗结束时测定单个骨骼肌纤维的收缩特性和线粒体ETC复合物的活性。与未处理的老龄大鼠相比，xjb处理的大鼠表现出更高的肌肉收缩力，这与肌肉匀浆和线粒体中蛋白质氧化的预防有关。xjab治疗的动物表现出呼吸复合物I、III和IV的高活性，而柠檬酸合酶活性没有变化。这些数据表明，线粒体ROS在肌肉无力中起因果作用，并且专门针对线粒体的ROS清除剂可以逆转与年龄相关的线粒体功能改变并改善骨骼肌的收缩特性。
Mitochondrial dysfunction plays a central role in the pathogenesis of sarcopenia associated with a loss of mass and activity of skeletal muscle. In addition to energy deprivation, increased mitochondrial ROS damage proteins and lipids in aged skeletal muscle. Therefore, prevention of mitochondrial ROS is important for potential therapeutic strategies to delay sarcopenia. This study elucidates the pharmacological efficiency of the new developed mitochondria-targeted ROS and electron scavenger, XJB-5-131 (XJB) to restore muscle contractility and mitochondrial function in aged skeletal muscle. Male adult (5-month old) and aged (29-month old) Fischer Brown Norway (F344/BN) rats were treated with XJB for four weeks and contractile properties of single skeletal muscle fibres and activity of mitochondrial ETC complexes were determined at the end of the treatment period. XJB-treated old rats showed higher muscle contractility associated with prevention of protein oxidation in both muscle homogenate and mitochondria compared with untreated counterparts. XJB-treated animals demonstrated a high activity of the respiratory complexes I, III, and IV with no changes in citrate synthase activity. These data demonstrate that mitochondrial ROS play a causal role in muscle weakness, and that a ROS scavenger specifically targeted to mitochondria can reverse age-related alterations of mitochondrial function and improve contractile properties in skeletal muscle.